Gutenberg Open Science

The Open Science Repository of Johannes Gutenberg University Mainz.

Visible. Citable. Open.

Recent Submissions

ZeitschriftenaufsatzAccess status: Open Access ,
A synthetic sponge system against miRNAs of the miR-17/92 cluster targets transcriptional MYC dosage compensation in aneuploid cancer
(2025) Bravo-Estupiñan, Diana M.; Geiß, Carsten; Arias-Arias, Jorge L.; Montaño-Samaniego, Mariela; Chinchilla-Monge, Ricardo; Marín-Müller, Christian; Quirós-Barrantes, Steve; Régnier-Vigouroux, Anne; Ibáñez-Hernández, Miguel; Mora-Rodríguez, Rodrigo A.
Background: Genomic instability, a hallmark of cancer, leads to copy number variations disrupting gene dosage balance and contributing to tumor progression. One of the most affected oncogenes is MYC, whose overexpression is tightly regulated to avoid cytotoxicity. In aneuploid cancer cells, gene dosage compensation mechanisms involving microRNAs (miRNAs) from the miR-17/92 cluster contribute in regulating MYC expression. Targeting this miRNA-mediated compensation system represents a promising therapeutic strategy leading to an uncontrolled and lethal MYC overexpression. Results: Synthetic miRNA sponges targeting miR-17, miR-19a, and miR-20a, key regulators of MYC dosage compensation, were designed and validated. Breast cancer cells (MCF7) with stable exogenous MYC overexpression were used to assess the impact of sponge constructs on MYC regulation. Quantitative RT-PCR revealed a significant reduction in miRNA expression and a corresponding increase in endogenous MYC levels upon sponge treatment. Functional assays in multiple colorectal cancer cell lines with varying MYC copy numbers demonstrated a time-dependent increase in cell death following sponge transfection. Cytotoxic effects increased with MYC copy number, confirming a correlation between gene dosage sensitivity and therapeutic response. Conclusions: Our findings demonstrate that miRNA sponges targeting the miR-17/92 cluster can effectively disrupt MYC dosage compensation, leading to selective cytotoxicity in MYC-amplified cancer cells.
ZeitschriftenaufsatzAccess status: Open Access ,
Barriers to suicide research are also barriers to suicide prevention : insights from conducting a mixed-methods project in oncology
(2025) Hirschmiller, Judith; Schwinn, Tamara; Wiltink, Jörg; Beutel, Manfred E.; Zwerenz, Rüdiger; Brähler, Elmar; Ernst, Mareike
Cancer patients are at risk for suicidal crises. There is a need for more research concerning specific risk/protective factors and knowledge about barriers and resources of prevention efforts in clinical practice. This contribution reports on difficulties during the realization of a research project that aimed to address these research gaps, among other approaches, via a patient survey and an interview study with healthcare professionals (HCPs). Throughout recruitment and implementation, we documented the barriers encountered and systematically analyzed them. We identified three main categories of obstacles toward the research endeavor that also hold meaning for the efficacy of suicide prevention: First, suicidal thoughts and behaviors are not (allowed to be) an issue in oncology, subsuming the denial of their occurrence, the minimization of their relevance, the alleged appropriateness of the construct to oncology, and the rejection of responsibility; second, prevailing suicide myths, in particular of iatrogenic harm; and third, strong, negative emotional reactions undermining dialogue. We interpret these experiences against previous considerations of dysregulated responses to suicidal patients in the healthcare setting and analyze their causes and functions. These findings highlight the urgent need for structured education on suicide prevention across medical disciplines, particularly in oncology. Addressing both knowledge gaps and emotional barriers among HCPs is crucial for fostering a proactive, evidence-based approach to suicide prevention. Future efforts should focus on integrating suicide risk assessment and intervention strategies into routine cancer care, alongside improved interdisciplinary collaboration and institutional support.
ZeitschriftenaufsatzAccess status: Open Access ,
Identification of nsp16 inhibitors of SARS -CoV-2, SARS -CoV-1 and MERS-CoV from FDA-approved drugs using in silico and in vitro methods
(2025) Omer, Ejlal A.; Abdelfatah, Sara; Shahhamzehei, Nasim; Guthart, Axel; Sutter, Kathrin; Schwarzer-Sperber, Hannah S.; Schwarzer, Roland; Efferth, Thomas
The methyltransferase nsp16 is a key enzyme that catalyses coronavirus replication. In this study, we virtually screened 1577 FDA-approved drugs against nsp16 of SARS-CoV-2, SARS-CoV-1, and MERS-CoV to identify compounds potentially serving as pan-coronavirus inhibitors. Microscale thermophoresis (MST) was used to verify the in-silico results obtained by virtual drug screening, followed by molecular docking and molecular dynamics simulation to test the binding affinities between the target and the candidates. Finally, the candidates were tested against a clinical isolate of SARS-CoV-2 in cell culture. The MST binding assay and molecular docking results showed that four of the candidates showed strong binding affinities to nsp16 of one or two coronaviruses. Nilotinib and simeprevir interacted with nsp16 protein of all three coronaviruses, viz., SARS-CoV-2, SARS-CoV-1, and MERS-CoV, suggesting their potential to act as pan-coronavirus inhibitors. The drugs inhibited the virus with IC50 values ranging between 8.34 and 36.1 µM when tested against a clinical isolate of SARS-CoV-2 in cell culture.